Novartis And Stemline Try For Fast-Track EU Review
Executive Summary
The European Medicines Agency is this week deciding whether it will fast track its review of orphan drugs that Novartis is developing for the treatment of Cushing's syndrome and Stemline Therapeutics is developing for the hematologic malignancy, BPDCN.
Novartis and Stemline Therapeutics will likely learn this week whether the EU marketing applications they plan to file for their investigational treatments for Cushing's syndrome and blastic plasmacytoid dendritic cell neoplasm (BPDCN) respectively will be granted fast-track review.
The companies’ requests for regulatory review via the European Medicines Agency’s accelerated assessment procedure are due to be considered by the EMA’s Committee for Medicinal Products for Human Use (CHMP) at its November meeting, which is under way in London. (Also see "Moment Of Truth For Pacritinib And Other EU Approval Hopefuls " - Pink Sheet, 12 Nov, 2018.) The Novartis product is osilodrostat (LCI699) and the BPDCN treatment, which appears to be from Stemline, is Elzonris (tagraxofusp, SL-401).
The fast-track mechanism can cut the time it takes the EMA to evaluate a marketing authorization application (MAA) for approval of a drug across the EU from up to 210 days to up to 150 days (not counting clock stops when applicants have to provide additional information).
Novartis And Osilodrostat
Novartis’s osilodrostat was granted EU orphan drug designation for the treatment of Cushing’s syndrome in 2014.
Cushing’s syndrome is characterized by an excess of the hormone cortisol in the blood. Its symptoms include weight gain affecting the face and torso but not the limbs, easy bruising, excessive growth of coarse hair on the face, weakening of the muscles and bones, depression, diabetes and high blood pressure. Osilodrostat blocks the action of the enzyme 11-beta-hydroxylase, which plays a part in the production of cortisol.
A Phase III clinical trial to confirm the efficacy and safety of osilodrostat for the treatment of patients with Cushing's disease who are candidates for medical therapy is underway and is expected to be completed in October next year.
Stemline’s Elzonris
The accelerated assessment request for Stemline’s Elzonris was filed by consultancy company TMC Pharma. Stemline is developing the biologic, tagraxofusp, for the treatment of adult patients with the hematologic malignancy, BPDCN.
Elzonris, which also has EU orphan drug status, is a targeted therapy directed to the interleukin-3 receptor present on a wide range of hematologic cancers. According to the company, four multicenter clinical trials of tagraxofusp are currently enrolling patients in a variety of indications, including a potentially pivotal Phase II trial in BPDCN.
Stemline is planning to submit its MAA to the EMA for Elzonris in the first quarter of 2019. In the US, the Food and Drug Administration has accepted for filing the company’s biologics license application (BLA) for Elzonris for BPDCN. The BLA has been granted priority preview (similar to accelerated assessment in the EU) and the FDA has set a target action date of Feb. 21, 2019, under the Prescription Drug User Fee Act.
The CHMP is expected to reach a decision on Novartis and Stemline’s requests for accelerated assessment at its Nov. 12-15 meeting. The EMA only discloses the outcomes in the minutes of the CHMP meeting at which the requests were considered; these are usually published at least six weeks later. Although companies may choose to reveal the result themselves before the minutes are published, they tend not to.
Major Public Health Interest
The EMA reserves accelerated assessments for products that are expected to be of major public health interest, particularly from the point of view of therapeutic innovation; refusal rates are high. (Also see "EU Accelerated Assessment Tracker: Second Half Trumps First By Far" - Pink Sheet, 7 Nov, 2018.) The agency says that requests for accelerated assessment should be made at least two to three months before the MAA is submitted.
These latest two requests will be added to the Pink Sheet EU accelerated assessment tracker in due course.
From the editors of Scrip Regulatory Affairs.